We propose to continue to study the significance of antiphospholipid antibodies (aPL), hematologic markers for increased risk of vascular thrombo-occlusive events, in ischemic stroke using the cost-effective and efficient strategy of collaborating with the WARSS (Warfarin Aspirin Recurrent Stroke Study) cohort--the continuation of the WARSS-APASS (Antiphospholipid Antibodies in Stroke Study) Collaborative Study. Based on current WARSS enrollment, 5 years of funding will be necessary to complete enrollment, follow-up, study closeout, and data analyses. aPL, seen in approximately 20% of first ischemic stroke patients in the WARSS cohort, may be a marker for increased risk of subsequent thrombo-occlusive events, including recurrent stroke. We wish to continue to combine scientific interests of WARSS and APASS. WARSS is a randomized and double-blind secondary stroke and death prevention trial comparing aspirin and warfarin in two treatment arms. The details of the WARSS-APASS collaboration have been worked out and use a mutually beneficial and highly cost effective strategy to assess aPL status in all WARSS patients. We are testing the hypothesis that a positive aPL status in the WARSS cohort will confer a higher risk of subsequent thrombo-occlusive events compared to WARSS patients who do not have aPL and who are matched to treatment arm. APASS requests continued support to obtain aPL status at baseline on all WARSS enrolled subjects and to document all thrombo-occlusive events. aPL status will also be documented yearly and at the time of a recurrent thrombo-occlusive event for all aPL(+) patients and one matched aPL(-) patient for each aPL(+) patient to ensure blinding of aPL status at each of the WARSS clinical centers. In addition, we believe that the important information obtained from this study could lead to a treatment trial potentially resulting in improved and more cost-effective health care for the subset of patients with stroke and aPL. This number is estimated to be at least 40,000 people per year in the United States. The cost to care for these patients, just in terms of acute health care dollars spent, is over $30 million, based on the Relative Index Scale. One could extrapolate similarly for myocardial infarction, deep venous thrombosis, systemic thromboembolic events and fetal loss (other thrombo-occlusive events linked to aPL). The number of people in the United States per year with this potentially treatable autoimmune-mediated syndrome is a major cause for concern and clearly demonstrates a need for further epidemiological study. There are benefits of linking APASS to WARSS, regardless of whether WARSS turns out to be a negative or a positive clinical trial for treatment differences. In addition, this is an opportunity to pioneer a new level of collaborative effort with great potential to benefit stroke victims, contribute significantly to our basic knowledge about stroke mechanism and save tax dollars.